P965: STEM-CELL MOBILIZATION WITH CYCLOPHOSPHAMIDE 4 G/M2 ALLOWS COLLECTION OF HIGH NUMBERS OF CD34+ CELLS AFTER DARA-VTD INDUCTION FOR MULTIPLE MYELOMA
Authors: Tommaso Perini, Carmine Liberatore, Girlando Virginia, Cecilia Passeri, Valeria Ferla, Ornella Iuliani, Alessia Orsini, Guido Montanaro, Francesca Farina, Alessandro DI Nicola, Sarah Marktel, Stefano Pulini, Stella Santarone, Patrizia Accorsi, Fabio Ciceri, Mauro DI Ianni, Magda Marcatti
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Quadruplet induction with Daratumumab, Bortezomib, Thalidomide and Dexamethasone (Dara-VTd) has become the standard treatment for transplant-eligible newly diagnosed multiple myeloma patients (NDMM). Despite improved response rates compared to VTd, concerns with stem-cell mobilization and collection emerged in CASSIOPEIA trial. Indeed, after a mobilization approach based on cyclophosphamide (2 to 3 g/m2) and granulocyte colony-stimulating factor (G-CSF) 10 μg/kg/day, patients treated with Dara-VTd experienced a greater use of plerixafor as well as a lower median number of collected CD34+ cells/Kg. Aims: Here we report our retrospective, multicenter experience on stem cell mobilization with cyclophosphamide 4 g/m2 and G-CSF after Dara-VTD induction. Methods: We retrospectively analyzed our real-life data on stem cell collection in 43 consecutive transplant-eligible NDMM patients treated with Dara-VTd in two Italian hospitals (IRCCS Ospedale San Raffaele, Milano; Ospedale Civile Santo Spirito, Pescara). Mobilization was performed with high-dose cyclophosphamide 4 g/m2 (HD-CTX) and G-CSF, either in an inpatient or outpatient setting according to center preference. Plerixafor 0,24 mg/kg was administered on demand as per institutional practice.The pre-planned collection target was 10 x 106 CD34+/kg. Results: Between December 1st, 2021 and February 28th, 2023, 43 NDMM completed Dara-VTd induction at our institutions, with a 98% overall response rate. After a median of 132 days (IQR 124 to 151 days) from start of induction, 42 patients received HD-CTX, of which 17 (39%) in an outpatient setting. Of these 17 patients treated in an outpatient setting, 3 (18%) had G3 febrile neutropenia requiring hospitalization, that promptly resolved after antibiotic treatment and leukocyte recovery. No other grade 3-4 adverse events were reported. Successful mobilization was reached in 39/42 patients (93%). Median number of cells collected was 10 × 106 CD34+/kg (IQR 9,01 × 106 to 11,48 × 106), with the lowest collection procedure yielding a total of 4,92 × 106 CD34+/kg. Total G-CSF administered per patient was 5,73 MU/kg +/- 2,07 (mean +/- SD). Median time from CTX to first day of apheresis was 11 days (IQR 10 to 13), with 27 patients (64,2%) needing 2 days of apheresis to complete cell collection (range 1-2). Plerixafor was needed in 18 patients (46%). 1 patient discontinued mobilization due to concomitant Sars-Cov2 infection and subsequent rescue attempts (chemo-free and CTX 2 g/m2 based) failed. 2 patients failed to mobilize adequate numbers of CD34+ and did not start the collection procedure: one was later mobilized with a chemo-free regimen, the other required a bone marrow harvest. 34/39 (87%) of NDMM patients who completed leukapheresis underwent transplant at time of data cutoff: number of infused CD34+ cells was 4,85 x 106 CD34+/kg +/- 1,2 (mean +/- SD). All patients obtained stable neutrophils and platelets engraftments after a median of 12 days (range: 9-14) and 16 days (range: 13-25), respectively. No unexpected toxicities were reported. Summary/Conclusion: Our data show that, after Dara-VTd, a mobilization regimen based on CTX 4 g/m2 and G-CSF allows the collection of high numbers of CD34+ cells and can be safely administered in the outpatient setting. CTX 4 g/m2 coupled with on-demand and patient-tailored usage of plerixafor is a valuable approach to achieve an optimal CD34+ cell collection after Dara-containing quadruplets, able to guarantee more than one autologous stem cell transplant and possible stem cell boosts in cases of prolonged cytopenia in subsequent therapies.Keywords: Multiple myeloma, Induction, Stem cell mobilization, Cyclophosphamide